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重组表达保守 M2 胞外结构域嵌合血凝素的减毒季节性流感 H3N2 病毒的广泛交叉保护。

Broad cross protection by recombinant live attenuated influenza H3N2 seasonal virus expressing conserved M2 extracellular domain in a chimeric hemagglutinin.

机构信息

Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, 30303, USA.

Department of Virology, Institute of Experimental Medicine, St Petersburg, Russia.

出版信息

Sci Rep. 2021 Feb 18;11(1):4151. doi: 10.1038/s41598-021-83704-0.

DOI:10.1038/s41598-021-83704-0
PMID:33603072
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7893060/
Abstract

Hemagglutinin (HA)-based current vaccines provide suboptimum cross protection. Influenza A virus contains an ion channel protein M2 conserved extracellular domain (M2e), a target for developing universal vaccines. Here we generated reassortant influenza virus rgH3N2 4xM2e virus (HA and NA from A/Switzerland/9715293/2013/(H3N2)) expressing chimeric 4xM2e-HA fusion proteins with 4xM2e epitopes inserted into the H3 HA N-terminus. Recombinant rgH3N2 4xM2e virus was found to retain equivalent growth kinetics as rgH3N2 in egg substrates. Intranasal single inoculation of mice with live rgH3N2 4xM2e virus was effective in priming the induction of M2e specific IgG antibody responses in mucosal and systemic sites as well as T cell responses. The rgH3N2 4xM2e primed mice were protected against a broad range of different influenza A virus subtypes including H1N1, H3N2, H5N1, H7N9, and H9N2. The findings support a new approach to improve the efficacy of current vaccine platforms by recombinant influenza virus inducing immunity to HA and cross protective M2e antigens.

摘要

血凝素（HA）为基础的当前疫苗提供次优的交叉保护。甲型流感病毒包含一个离子通道蛋白 M2 保守的细胞外结构域（M2e），这是开发通用疫苗的一个目标。在这里，我们生成了重组流感病毒 rgH3N2 4xM2e 病毒（HA 和 NA 来自 A/Switzerland/9715293/2013/（H3N2）），表达嵌合的 4xM2e-HA 融合蛋白，其中 4xM2e 表位插入到 H3 HA N 末端。发现重组 rgH3N2 4xM2e 病毒在鸡蛋基质中保留了与 rgH3N2 相当的生长动力学。通过鼻腔内单次接种活 rgH3N2 4xM2e 病毒，可有效地在黏膜和全身部位诱导 M2e 特异性 IgG 抗体反应和 T 细胞反应。rgH3N2 4xM2e 引发的小鼠对广泛的不同甲型流感病毒亚型包括 H1N1、H3N2、H5N1、H7N9 和 H9N2 具有保护作用。这些发现支持了通过重组流感病毒诱导对 HA 和交叉保护 M2e 抗原的免疫来提高现有疫苗平台疗效的新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b01d/7893060/8bb88a5da336/41598_2021_83704_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b01d/7893060/c8ed618e5ffa/41598_2021_83704_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b01d/7893060/885dbf52887f/41598_2021_83704_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b01d/7893060/32c5b69dabac/41598_2021_83704_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b01d/7893060/af728ccf4b31/41598_2021_83704_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b01d/7893060/ffb6702db115/41598_2021_83704_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b01d/7893060/cf22a61143cf/41598_2021_83704_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b01d/7893060/7628e91037f0/41598_2021_83704_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b01d/7893060/8bb88a5da336/41598_2021_83704_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b01d/7893060/c8ed618e5ffa/41598_2021_83704_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b01d/7893060/885dbf52887f/41598_2021_83704_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b01d/7893060/32c5b69dabac/41598_2021_83704_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b01d/7893060/af728ccf4b31/41598_2021_83704_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b01d/7893060/ffb6702db115/41598_2021_83704_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b01d/7893060/cf22a61143cf/41598_2021_83704_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b01d/7893060/7628e91037f0/41598_2021_83704_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b01d/7893060/8bb88a5da336/41598_2021_83704_Fig8_HTML.jpg

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